Mesenchymal Stem Cell-Derived Exosomes Modulate Chondrocyte Glutamine Metabolism to Alleviate Osteoarthritis Progression.
Mesenchymal Stem Cell-Derived Exosomes Modulate Chondrocyte Glutamine Metabolism to Alleviate Osteoarthritis Progression.
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DOI：
10.1155/2021/2979124
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发表时间：
2021
影响因子：
4.6
通讯作者：
Mao X
中科院分区：
文献类型：
--
作者：
Jiang K;Jiang T;Chen Y;Mao X
骨关节炎（OA）在65岁以上人群中发病率很高，目前还没有药物可以完全治愈它。本研究旨在研究外泌体在OA治疗中调节谷氨酰胺代谢的作用。首先，我们鉴定了从小鼠OA模型骨髓间充质干细胞（MSC）中提取的外泌体。在体外实验中，与对照组相比，OA组细胞凋亡增加，OA组细胞增殖受到抑制。外泌体处理后，细胞凋亡和细胞增殖逆转。OA组炎症因子（TNFα, IL-6），谷氨酰胺代谢活性相关蛋白（c-MYC, GLS1），谷氨酰胺和GSH/GSSG均升高。c-MYC的过表达降低了外泌体的治疗效果。同时，我们发现在外泌体的作用下，软骨细胞功能因子（collagen II, Aggrecan）得到改善。然而，e-c- myc逆转了外泌体的治疗作用。在体内，我们发现OA组小鼠的跑步能力下降，软骨组织严重受损。此外，OA组TNFα、IL-6和软骨细胞凋亡增加，而II型胶原、聚集蛋白和谷氨酸的代谢降低。外泌体处理后，小鼠的运动能力、组织损伤、炎症和软骨细胞功能得到改善，谷氨酸代谢增加。本研究表明外泌体通过调节c-MYC调节软骨细胞谷氨酰胺代谢水平，从而缓解OA。
Osteoarthritis (OA) had a high incidence in people over 65 years old, and there is currently no drug that could completely cure it. This study is aimed at studying the role of exosomes in regulating glutamine metabolism in the treatment of OA. First, we identified the exosomes extracted from the mouse OA model's bone marrow mesenchymal stem cells (MSC). In vitro, compared with the control group, the cell apoptosis in the OA group increased, while the cell proliferation of the OA group was suppressed. After exosomal treatment, cell apoptosis and cell proliferation were reversed. Inflammatory factors (TNFα, IL-6), glutamine metabolic activity-related proteins (c-MYC, GLS1), glutamine, and GSH/GSSG were increased in the OA group. The overexpression of c-MYC reduced the therapeutic effect of exosomes. At the same time, we found that chondrocyte functional factors (collagen II, Aggrecan) were improved under the treatment of exosomes. However, oe-c-MYC reversed the therapeutic effect of exosomes. In vivo, we found that the running capacity of the mice in the OA group was reduced, and the cartilage tissue was severely damaged. In addition, TNFα, IL-6, and chondrocyte apoptosis increased, while the metabolism of collagen II, Aggrecan, and glutamate decreased in the OA group. After exosomal treatment, the mice's exercise capacity, tissue damage, inflammation, and chondrocyte function were improved, and glutamate metabolism was increased. This study showed that exosomes regulated the level of chondrocyte glutamine metabolism by regulating c-MYC, thereby alleviating OA.
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